Restricted clonality and crossreactive idiotypes

Cold agglutinins have been the subject of considerable interest since the late 1950s when it was realized that they are usually monoclonal or oligoclonal antibodies. Those occurring in chronic cold agglutinin disease are almost always monoclonal, but even the transiently occurring, postinfective cold agglutinins, when isolated with care to avoid contamination with serum immunoglobulins, have been found to be monoclonal or oligoclonal antibodies. Cold agglutinins with anti-I and anti-i specificities are almost always of the IgM class; the majority have k light chains, and only a minority, X. Cold agglutinins with other specificities, designated anti-Pr, anti-Gd, anti-F1 etc. occur less commonly. The majority of these are also of the IgM class but several monoclonal IgA and IgG have been described.

There is a predominance of k light chains among monoclonal anti-I, whereas \ chains are not uncommon among anti-i and other types of cold agglutinin. Cold agglutinins were the first antibodies among which cross-reactive idiotypes were demonstrated. Two distinct idiotypic systems have been described: one found among anti-I and anti-i, and a second among anti-Pr antibodies; the latter included proteins of the IgM and IgA classes. The first demonstration of idiotypic antigens on blood lymphocytes corresponding to those serum antibodies in the same individuals was made in patients with cold agglutinin disease. The idiotypic antigens among anti-I and anti-i are located predominantly on the variable regions of their heavy chains. Restricted Vn and V,. subgroups are represented among these antibodies, and the cross-reactive idiotypes are almost certainly associated with the framework rather than the complementarity determining regions, since an occasional myeloma protein lacking erythrocyte cold agglutinin activity also has been found to express the same idiotypic determinants.

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